JP4137998B2 - Powder coating composition for electrostatic coating of pharmaceutical substrates - Google Patents

Abstract

A method of coating a pharmaceutical substrate, especially a tablet core, wherein a pharmaceutically acceptable powder coating material comprising active material is electrostatically applied to a surface of the substrate, wherein the coated substrate constitutes a dosage unit; and a powder coating material suitable for use in the electrostatic powder coating of a pharmaceutical substrate, in which the material is pharmaceutically acceptable, is treatable to form a film coating and includes composite particles, the composite particles comprising two or more components having different physical and/or chemical properties, the material comprising active material. The pharmaceutical substrate may contain the same active material as the powder coating material or may contain a different active material from the powder material or may contain no active material.

Description

The present invention relates to electrostatic coating of a pharmaceutical substrate with a powder coating material and powder coating material for coating a pharmaceutical substrate. In particular, the present invention relates to, but is not limited to, electrostatic coating of pharmaceutical tablet cores with powder coating materials and powder coating materials for pharmaceutical tablet core coatings. Reference is made to pharmaceutical tablets throughout the specification, and in particular, the present invention is often viewed as an application relating to conventional shaped pharmaceutical tablets, but this term refers to other products taken orally such as pellets, capsules and globules. Should be interpreted in a broad sense that also includes
Electrostatic coating of conductive substrates such as metal objects is well known. For example, in some paint spraying methods, the paint is charged and sprayed onto a metal object that is grounded. This method has been successful in forming a uniform coating film on a substrate.
Electrostatic coating of non-conductive substrates, especially pharmaceutical tablet cores, is quite difficult. For years, proposals have been made on electrostatic coating of tablets. For example, UK 1075404 proposes a device for tablet coating, in which fine particles of the coating solution are sprayed onto the tablets using a sprayer in a high potential field. As an example, the coating is dried using an infrared heater. However, this proposal has never been practiced on a substantially industrial scale, and the coating of pharmaceutical tablet cores is usually carried out batchwise by applying a liquid paint in a rotating drum. This liquid coating material may be supplied in powder form in some cases, but even if so, the coating material is used after being dissolved or dispersed in the liquid. Therefore, the coating material is not applied to the tablet core in powder form.
Application of liquid coating to pharmaceutical tablet cores is often easier than powder coating. It is difficult to fix the powder to the tablet, and in order to fix the coating to the core, it is necessary to convert the powder into a thin film without damaging the tablet core, which usually contains organic materials. Furthermore, uniform coating is required, and it is difficult to obtain a uniform powder coating on the tablet core.
If liquid paint is used, the paint must be dried. Theoretically, drying can be carried out at room temperature in some environments, however, tablet heating is important in the industry in terms of the speed at which the process is carried out, and the solvent used for liquid coating is evaporated. This is expensive because of the large amount of energy required. Another disadvantage of liquid coating is that useful liquids, preferably materials that do not dissolve or disperse properly in water, cannot be used for the coating material.
WO92 / 14451 relates to electrostatic powder coating of pharmaceutical tablets. The pharmaceutical tablet core is transported on a grounded conveyor belt, and electrostatically charged powder is sprayed toward the core to adhere to the core surface. Explains and illustrates how to form a powder coating. Thereafter, the powder coating is melted to give a molten film coating fixed to the core.
The disadvantage of such a method is that most of the powder sprayed towards the core is not charged and does not deposit on the core. This leads to waste of spray droplets and powder material, and makes it difficult to achieve uniform coating.
In a first aspect, the present invention attempts to provide a powder coating material suitable for electrostatic powder coating of pharmaceutical tablet cores, and provides a method for electrostatic coating of pharmaceutical tablet cores by using special powder coating materials. Attempts to facilitate electrostatic coating.
The first aspect of the present invention is to provide a powder coating material for use in electrostatic powder coating of tablet cores, particularly for coating methods defined below, and having special properties that give suitability for use in this method. It is. Preferably, the special properties of the powder coating material are defined below, and since the advantages afforded by these properties are influenced by the coating method employed, this method is also defined.
According to a first aspect of the present invention, the present invention provides a powder coating material suitable for electrostatic powder coating of a pharmaceutical tablet core, the material being pharmaceutically acceptable, capable of thin film coating processing, and Comprising composite particles, said composite particles being composed of two or more components having different physical and / or chemical properties.
It is important that the powder coating material is a pharmaceutically acceptable material. This in itself imposes severe constraints on powder coating materials, at least most of the powder coating materials commercially available for electrostatic powder coating processing are physiologically unacceptable and pharmaceutical tablets Commercially available materials for the core coating material are generally not suitable for electrostatic powder coating because of other inappropriate material properties.
The powder coating material of the present invention includes at least two different components, each having different physical and / or chemical properties. The use of a material composed of one or more components compared to the use of a one-component material makes it much easier to provide a powder material having the desired properties described above and elsewhere in the specification. For powder materials containing two or more extraneous components, we have found that improved coating is achieved when the powder contains several component composite particles.
If the coating method used is, for example, as described in the examples below, one or more coating material particles will be present if one or more of the components does not have the electrical properties required for coating on the core. It is particularly important to contain these components. If the particles are not composite particles, these particles consisting of components that do not have the required electrical properties may simply stay in the powder source and not be coated on the tablet core.
As used herein, the term “composite particle” refers to a particle formed from two or more different components. The composite particles are not homogeneous, and the composite particles have two or more regions each composed of fine particles of different components. The composite particles may be in the form of individual separate composite particles or may be agglomerates or aggregates of individual particles of different components, where the agglomerates or aggregates exhibit the behavior of separate composite particles. .
Advantageously, at least 50% by weight of the powder particles are composite particles. Ideally, virtually all particles need only be composite particles, which is not possible, especially when the particle size of the composite particles is small. If the powder includes two or more components having different physical and / or chemical properties, the composite particles advantageously also include other components. Ideally, virtually all composite particles are composed of individually separated particles that contain each of the heterogeneous components. However, in practice, satisfactory coating is obtained when the individual component particles form composite particles as aggregates or agglomerates.
Preferably two or more components are processed simultaneously. This simultaneous treatment consists of granulation, spray coagulation, spray drying or simultaneous grinding. If this co-treatment results in a relatively large size, for example granules, it is advantageous in some cases to carry out a subsequent grinding step to reduce the particle size. You may implement a miniaturization process newly.
As is well known, mixing of powder components usually results in a uniform mixture of components. However, in special cases, composite particles can be obtained by a mixing method by carefully selecting the mixing conditions, such as the initial particle size of the components and the mixing means.
According to the first aspect of the present invention, the powder coating material is a material that can be coated on the surface of the tablet core and then processed to form a thin film coating fixed to the core. Thus, the coating method of the present invention includes a step of forming a thin film coating fixed on the tablet core surface by processing the powder after coating the tablet core surface with powder. The thin-film coating is advantageously continuous, in which case the coating is not divided into separate parts, but there are small gaps that are not visible to the naked eye, for example, between the coating particles fixed together during the processing process. Existing. Thus, the paint is sintered. For some applications, it is preferred that no gaps exist in the thin film coating and / or that it be substantially homogeneous.
The powder material initially deposited on the tablet core is often easily removed by simply weakly adhering to the substrate surface. Because the mechanical strength of the tablet core itself is often small, the treatment to form a thin film coating is particularly advantageous when coating a pharmaceutical tablet core, and a thin film coating is used to provide strength, and the coated tablet To withstand the next process such as packaging and unpacking. Thin film coating can give the tablet core special strength, but is often very weak when separated from the core surface. The tensile strength of thin film coating as a free thin film is, for example, 8MNm^-2Or less, and TiO in the coating material₂It was found that the tensile strength decreased with increasing amount of.
When the tensile strength of the free thin film is small, it is particularly important that the thin film has a cohesive coating on the core surface with excellent adhesion to the tablet core.
When the powder material is converted into a liquid phase in the thin film coating forming step, the viscosity of the powder material in the liquid phase is preferably 500 Pascals or less, more preferably 75 Pascals or less.
It is an advantage that the powder coating material can be processed at a temperature of 250 ° C. or less, more preferably 200 ° C. or less, for forming a thin film coating. Conveniently, the powder coating material can be melted at a temperature below 250 ° C., more preferably below 200 ° C. under atmospheric pressure. It is important to process the powder without damaging the tablet core to form a coating around the tablet core, and this is due to the fact that many tablet cores containing organic materials are heat sensitive, so It imposes demands on it. The powder coating material preferably has a melting point in the range of 50C to 180C, more preferably in the range of 60C to 100C. For materials exhibiting a glass transition, the powder coating material preferably has a softening point in the range of 30 ° C to 180 ° C.
The above requirements place additional constraints on powder coating materials. Many materials do not melt and are carbonized by heat. Other materials that are meltable, however, need to be exposed to a heat source for a long time for melting, thus significantly increasing the risk of damage to the core and the time to form a thin film on the core. Unacceptable for economic reasons.
The desired temperature at which the powder coating material can be processed will, of course, depend on the material from which the tablet core is made, and for some materials the processing step may include temperatures above 250 ° C. In such cases, the exposure time to such high temperatures is reduced.
Preferably, the powder treatment to form the thin film coating includes a heating step, preferably a heating step using infrared radiation, and electromagnetic radiation, electromagnetic conduction, or electromagnetic induction can be used in other forms. The processing of the powder material can be carried out with partial or total pressure reduction around the tablet core. The change in powder material during processing is a simple physical change from solid to liquid and from cooling to a continuous solid film. Recently, powder materials can include polymers that can be cured during processing, such as polymers that cure by gamma radiation, ultraviolet light, or radio frequency energy irradiation to form a crosslinked polymer film.
We have found that the particle size of the powder coating material has a particularly important influence on the behavior of the material in the electrostatic powder coating process. It is advantageous that the particle size of the material is small. It is preferred that at least 95% by volume and at least 90% by volume of the powder material particles have a particle size of 50 μm or less. The term “particle size” refers to the corresponding particle diameter of a particle and can be measured, for example, using laser light diffraction.
Where the relevant particles are composite particles comprising agglomerates or aggregates of particles, the particle size is the size of the composite particles, not the size of individual particles in the agglomerates or aggregates.
Such particle sizes are remarkably small as coating materials for pharmaceutical tablet cores, and in fact, such small particle sizes are recognized as having the drawback of making the materials difficult to manufacture and handle due to their cohesiveness. Has been. However, we have found that the coating of pharmaceutical tablet cores by electrostatic coating methods has particular advantages in adopting small particle sizes and that there are additional advantages by eliminating the drawbacks. For example, the high surface to mass ratio provided by small particles increases the electrostatic force on the particles compared to the inertial force.
Increasing the electrostatic force has the advantage of increasing the force on the particle, which causes the particle to move into contact with the tablet core, while decreasing the inertial force reduces the force required to accelerate the particle and moves backward with the core. Reduces the possibility of particles that bounce and reach the tablet core. We have found that it is particularly advantageous when particles of at least 90% by volume of the powder material have a particle size of 20 μm or less. Preferably, at least 95% by volume of the powder material particles have a particle size of 30 μm or less.
In particular, for selected powder materials, if the particles tend to bounce off the surface of the tablet core, hold the tablet core in close proximity to the powder material source after applying the pretreatment composition to the surface of the tablet core. Let The pretreatment composition was able to improve particle capture by the core surface and enabled the use of large particles as large as 750 μm as the coating material. A liquid can be used in the pretreatment composition to increase the force acting on the particles and keep the particles on the core. When pretreatment is employed, preferably at least 90% by volume of the particles are 300 μm or less in size, and preferably at least 50% by volume of the particles are 200 μm or less in size.
When the particle size becomes very small, the difficulty in handling the powder becomes severe. Thus, it is advantageous that at least 50%, preferably at least 75%, optimally 90% by volume of the powder has a particle size of at least 5 μm.
In one preferred powder coating material, the average particle diameter is about 10 μm and does not include particles having a diameter substantially greater than 100 μm.
Suitably, at least 30% by volume of the powder particles have a particle size in the range of 5 μm to 25 μm.
We have found that it is also particularly important that the powder particles have a narrow range of particle sizes. Preferably at least 30 wt%, more preferably at least 75 wt% of the particles are in the range x to 2x, more preferably in the range x to 1.5x, optimally in the range x to 1.25x. Has a particle size, where x represents the particle size of the powder.
For example, in a powder having relatively small size particles, preferably at least 30% by weight of the particles are in the range of 10 μm to 20 μm, more preferably in the range of 10 μm to 15 μm, optimally in the range of 10 μm to 12.5 μm. Have a particle size of
If the particles are relatively large, for example pretreatment as described above, the preferred relative variation in particle size is usually smaller than for relatively small size particles.
We have found that powders with a large particle size range are disadvantageous compared to powders with a small particle size range for performing a good uniform application of the powder on the tablet core and from core to core. It was. This is thought to be because particles having a certain particle size are preferentially painted on the tablet core when compared to smaller or larger sized particles. This means that there is a difference in the quality of the coating of the core and the change in the quality of the coating, with one painted core painted with a powder material of a newly tailored batch and another painted core coated relatively later in the same batch. It is connected.
Moisture content of powder coating material not more than 10% by weight, preferably not more than 5% by weight, more preferably not more than 3% by weight, based on the weight of the powder coating material (measured by moisture loss during drying) It is convenient to have
There are several different electrostatic effects, and in accordance with the first aspect of the present invention, can be used in electrostatic coating methods using powders to coat pharmaceutical tablet cores, and several different powders that are particularly adapted to the utilization of different effects. Has electrical characteristics. Three different effects and related properties of the powder are described here, and it must be appreciated that each can be used independently of the other or in connection with one or more of the other.
The first possibility is to induce a temporary dipole in the particles of the powder, after which the particles become tablet cores due to the interaction of the dipole with the electric field in the region between the powder source and the tablet core. Led in the direction of. Preferably the coating material is 10⁸-10¹⁶Has a specific resistance in the range of Ωm.
A second possibility is to apply a net charge to the powder particles. This net charge is introduced triboelectrically or by corona charging. Therefore, the coating material is preferably receptive to such a net charge and can retain the charge (long enough to guide the material well onto the tablet core).
A third possibility is to give the powder particles a permanent or semi-permanent dipole. Such “electrets” will be directed in the direction of the tablet core by the interaction of the electric field acting on the area between the powder source and the tablet core. Thus, the coating material may include an electret.
A fourth possibility is to provide a magnetic dipole in the powder material using iron or other magnetic material or paramagnetic material.
It is preferred that the powder material can be directed to the tablet core without depending on the overall net charge applied to the powder material and without depending on the permanent implant charge in the powder material. Thus, it is preferred that the powder material be sensitive to movement under the action of electrostatic forces, which sensitivity is measured by the tests specified below.
To determine whether a powder material is sensitive to movement under the influence of electrostatic forces, the following test is performed.
A sample of 0.5 g of powder material is taken and placed on a conductive metal plate placed horizontally and kept at ground potential in an environment with a relative humidity not greater than 65%. This powder material is expanded to a thickness close to a monomolecular layer. After the powder material is left in that state for 30 minutes, a round metal probe with a diameter of 5 mm is placed 10 mm above the center of the powder material, the high voltage is first +10 KV, then -10 KV (current limited to about 5 μA) ) And apply to the probe for about 10 seconds. If the particles of the powder material that represent the material as a whole are attracted upward and contact the probe during either high voltage application, the test results show that the powder material moves under the action of electrostatic force. To be sensitive to. If the particles of the powder material are not attracted upwards and do not contact the probe, or if only certain particles are attracted and the attracted particles are not representative of the material as a whole, the test result is The powder material will not be sensitive to movement under the action of electrostatic forces.
The sensitivity of the powder material naturally depends on the combination of the electrical properties of the powder and other physical properties such as the particle size of the powder.
In order for the particles of the coating material to be charged (eg, triboelectrically) and adhere to the core surface, it is particularly advantageous for the particles to be substantially all of the same symbolic charge. It has been found that an unsatisfactory coating forms on the core surface when a group of particles contains a mixture of positive and negative charges. When the powder is charged, it is preferable that the powder is composed of a composition in which the whole powder has substantially the same symbol charge. Furthermore, if the particles are not of the same symbolic charge, the powder material is oversprayed, reducing the efficiency of the painting process. It is also preferred that most particles have substantially the same charge.
Since the material consists of more than one component, the properties of the powder material can be altered by adjusting the relative proportions of the components. In general, when referring to the properties of a powder material, that property is the property exhibited by the material as a whole, and that one or more components of the material do not exhibit that property alone. . However, it is satisfactory if one or several components of the powder coating material, rather than the powder coating material as a whole, exhibit the following properties: for example, forming a thin film coating at low temperatures The advantages of the material are achieved by only one of the two or more components of the material exhibiting its properties; other components remain solid particles and are larger than particles that convert to a thin film coating. In such a case, there is a substantial variation in the particle sizes of the two components; for example, particles converted to thin film coating have a particle size in the range of 5-20 μm, while solids The particles that remain as particles are substantially larger.
One of the extraneous components may serve to provide the necessary electrostatic properties to the powder material. For example, one extraneous component is triboelectrically and / or coronaally charged and / or becomes an electret or magnet and / or under the action of electrostatic forces as defined in the tests described herein. May be sensitive to movement.
The chemical properties of the powder material are important for the efficiency and appearance of forming the paint.
When discussing the chemical properties of a material, it is advantageous to process a material composed of multiple components, and as will be apparent from the discussion below, the same compound is used as one or more components, and therefore a powder. References in the following description relating to the material consisting of two or more components require that two or more dissimilar components are necessarily present, unless the components are specifically considered different. Should not be considered.
The powder material preferably contains a first component that can be melted at a temperature of 250 ° C. or lower, more preferably 200 ° C. or lower to form a continuous thin film on the core surface. As discussed above, melting can take the form of melting, softening or crosslinking of the first component within the above temperature range.
It is preferred that the first component is substantially soluble in the aqueous medium. Usually, the first component is soluble in a neutral aqueous medium and only dissolves in a selected PH range, such as PH3 to PH6, or PH8 to PH14.
Preferably, the first component consists of polyoxyethylene, sugar alcohol, and one or more of unsaturated or saturated fatty acids and esters. The first component can include a cellulose derivative that melts at a temperature of 250 ° C. or lower, such as hydroxypropylcellulose. Not all cellulose derivatives can be used as the first component, for example hydroxypropylmethylcellulose does not have the required melt properties and carbonizes upon heating.
The first component can include polyethylene glycol, which has good melt properties and can form a good continuous thin film on the substrate surface after processing.
A suitable sugar alcohol is xylitol, which material has suitable electrical properties and melts at a suitable temperature and is useful as a coating material in the coating of pharmaceutical tablet cores.
Other materials that can be used as the first component include waxes and oils, wax or oil alcohols, poloxamers, alkylnaphthalenes such as diethyl phthalate, citric acid and esters. When the powder component is a liquid, the component can simply be added to the other components in liquid form and may be provided with a carrier material, for example in powder form.
Other compounds with suitable melting properties may exist and the above is merely exemplary.
The first component may consist of exactly one compound or may contain two or more compounds.
In many cases, the component with the most desirable melt properties does not provide the optimal electrical properties and / or does not provide the desired finish, coating or appearance of the paint. Therefore, it is preferable to use the second component having the necessary electrical characteristics as described above.
However, it should be understood that the first component may have the desired electrical properties of the second component, and the second component may have the desired melting properties of the first component.
The second component includes acrylic acid, polymers and copolymers of acrylic acid and derivatives thereof such as polymethyl acrylate, polyalkene and derivatives thereof, esters, aryl esters and derivatives thereof, polyvinyl alcohol and esters, cellulose and derivatives thereof such as cellulose It consists of one or more ethers and cellulose esters (crosslinked or non-crosslinked), such as ethyl cellulose, one or more enteric polymers such as cellulose acetate phthalate and hydroxypropyl methylcellulose phthalate. The second component is one of one or more biodegradable polymers such as polylactide, polyglycolide, polyhydroxybutyrate, polyhydroxyvalerate, ethylene vinyl acetate copolymer, and polyanhydride (homo or heteropolymer). One or more may be included. The second component may be polyethylene oxide.
As already mentioned, the first component and the second component may contain the same compound, but in many cases the first and second components are different compounds. For example, the first and second components may each contain xylitol, but in this case a viscosity modifier and a crystallization inhibitor should be added to give the second component the desired melt characteristics.
Preferably, the coating material comprising two or more extraneous components includes a dispersant component that improves the dispersion of the extraneous components. The dispersant component is preferably an anionic, cationic or nonionic surfactant, but may be other compounds which are not usually called surfactants but have similar effects. The dispersant component may be a co-solvent.
The dispersant component may be, for example, one or more of sodium lauryl sulfate, docusate sodium, tween (sorbitan fatty acid ester), poloxamer, and cetostearyl alcohol. Like the first and / or second component compounds, the dispersant component may comprise the same compound. As described above, both the third and first components may include a poloxamer. It is preferred that the material comprises at least 1%, preferably 2-5% by weight of a dispersant component, based on the weight of the material.
It is advantageous for the powder coating material to contain an anti-friction component to reduce frictional forces and / or other forces between the powder coating material particles and improve the flowability of the powder. Anti-friction components include titanium dioxide, colloidal silica, talc or starch, or mixtures thereof.
When the coating material is used in “immediate” release tablets, it is advantageous that the powder coating material includes a disintegrant that can break the coating. In the case of a coating on the tablet core, the inclusion of a disintegrant during coating accelerates the disintegration of the coating immediately when the tablet is ingested.
Disintegrants are those that swell rapidly and strongly when contacted with moisture, thereby destroying the coating. Some disintegrants swell and become 40 times their original volume within seconds. Examples of suitable disintegrants are starch glycolic acid sodium salt (cross-linked) and carboxymethylcellulose sodium salt (cross-linked).
Alternatively or in addition, the disintegrant may be a wicking type, which allows moisture to penetrate through the coating into the tablet core, but prevents back-flow of moisture through the coating from the tablet core and thereby destroys the coating. Examples of suitable wicking type disintegrants are natural starch, cross-linked polyvinyl pyrrolidone (CrossProvidone).
The disintegrant may be a gas generating type such as sodium carbonate, sodium bicarbonate and sodium glycinate.
Preferably, the powder coating material contains up to 10% by volume of disintegrant. Preferably, the powder contains 5 wt% or less, preferably 2 wt% or less, more preferably 1 wt% or less, and optimally about 0.5 wt% disintegrant.
Preferably, the powder coating material further contains one or more opacifiers such as titanium dioxide and talc. Preferably, the material comprises 50 wt% or less, preferably 40 wt% or less, more preferably 30 wt% or less, and most preferably about 10 wt% or less of the opacifier based on the weight of the material.
Preferably, the powder coating material further comprises one or more colorants, such as metal oxides or lakes, such as aluminum lakes, iron oxides, dyes, and one or more taste modifiers, such as aspartame, acesulfame. k, cyclamate, saccharin, sugar, sugar alcohol or flavoring agents, and the like. Preferably, the material comprises 10% by weight or less, preferably 1-5% by weight, based on the weight of the material, and preferably 5% by weight or less, based on the weight of the material. More preferably, it contains 1% by weight or less of a flavoring agent. When the flavoring agent is a sweetener, preferably the material contains 0.5% by weight or less of the sweetener. Preferably, the material comprises 5% by weight or less of colorant and flavor based on the weight of the material. It will be appreciated that the anti-friction component, opacifier, colorant and taste modifier may be the same compound as the other component compounds of the powder coating material.
Powder coating materials can contain bioactive materials, which are materials that increase or decrease process speed in a biological environment. The bioactive material may be a physiologically active material. The coating material containing the active material can be applied, for example, to a tablet core containing the same or different active material, or to a non-active material containing tablet core. The active material can contain one or more compounds. Active materials include acid digestion and exercise inducers, laxatives, antidiarrheals, colon and rectal drugs, pancreatic enzymes and bile acids, antiarrhythmic drugs, antianginal drugs, diuretics, antihypertensive drugs, anticoagulants, anticoagulants Thrombotic drugs, fibrinolytic drugs, hemostatic drugs, fat deficiency drugs, anti-anemic / neutropenic drugs, hypnotics, anti-anxiety drugs, antipsychotic drugs, antidepressants, antiemetics, antispasmodics, CNS stimulants, analgesia Drugs, antipyretic drugs, anti-migraine drugs, non-steroidal anti-inflammatory drugs, anti-ventilants, muscle relaxants, neuromuscular drugs, steroids, hypoglycemia drugs, hyperglycemia drugs, diagnostic drugs, antibiotics, antifungal Drugs, antimalarial drugs, antiviral drugs, immunosuppressive drugs, nutritional drugs, vitamins, electrolytes, appetite suppressants, appetite suppressants, bronchodilators, expectorants, antitussives, mucolytic drugs, decongestants, antiglaucoma Including drugs, oral contraceptives, and / or anti-neoplastic agents.
Tablet cores to which the powder coating material is applied usually contain one or more inert chemicals. Inert chemicals include diluents such as lactose, sucrose, glucose, starch, cellulose, microcrystalline cellulose; binders such as polyvinylpyrrolidone, starch mucus, gelatin, gum arabic; disintegrants such as cross-linked carboxymethylcellulose sodium salt, Sodium starch glycolate, crosslinked polyvinylpyrrolidone; Lubricants such as magnesium stearate, sodium stearyl fumarate; glidants such as colloidal silica, talc; surfactants such as wetting agents, sodium lauryl sulfate, docusate sodium; coloring Agents; can include flavoring agents and / or gas generants such as sodium bicarbonate and citric acid.
The tablet core can also include one or more of the active materials listed above. Preferably, the powder coating material comprises at least 0.5% by weight of active material, more preferably 1% by weight, based on the weight of the powder coating material. For example, a 10 mg coating on a tablet can contain approximately at least 0.05 mg of active material.
The ratio of mixing the components of the powder coating material largely depends on the properties of the material constituting the powder coating material and the substrate to be coated. The ratio is adjusted to achieve the desired electrical and melting characteristics. Usually, the powder coating material contains at least 10%, preferably at least 15%, optimally about 20% by weight of the first component. Usually, the powder coating material contains at least 10% by weight, preferably at least 20% by weight, and more preferably at least 40% by weight of the second component, in each case based on the weight of the powder coating material. Preferably, the weight ratio of the second component to the first component is about 3: 1. The component ratio depends on the materials constituting the first and second components. The ratio is 2: 1 or 1: 1.
The present invention further provides a coating material for electrostatic coating of a pharmaceutical substrate, the coating material containing an active material. As indicated above, the coating material containing the active material is applied to a tablet core containing, for example, the same or different active material, or applied to a core containing an inactive material.
When trying to manage a very small dose of active material in tablet form, the active material is mixed with a large amount of non-active “fill” material to create a manageable size tablet. Traditionally, the active material and the filling material were simply mixed together and the intake of the resulting mixture was tableted. It has been found that accurate management of the amount of active material contained in each tablet is difficult, and the uniformity of intake is insufficient. This was especially observed when the amount of active material required by each tablet was small.
It has been found that by applying the active material to the tablet surface, a very small amount of active material can be accurately applied to the tablet and the reproducibility of the intake can be improved.
The amount of active material contained in the coating material will of course depend on the amount of active material intake applied to the substrate and the thickness of the coating formed. Usually, the material contains at least 0.5% by weight of active material, based on the weight of the coating.
Conveniently, the coating material is a powder coating material. It is therefore convenient to apply the coating material using a method similar to that described above, and the coating material is applied to the substrate accurately and without overspraying.
Preferably, the coating material containing the active material contains at least 90% by volume of particles having a particle size not greater than 50 μm. Preferably, at least 90% by volume of the powder particles have a particle size of 30 μm or less, more preferably 20 μm or less.
The present invention also provides the use of a coating material comprising an active material in electrostatic coating of a substrate, particularly in the electrostatic coating of a pharmaceutical tablet core.
The first aspect of the present invention also provides a method of electrostatically coating a pharmaceutical tablet core with a powder material, and a powder material as defined above.
Furthermore, the 1st viewpoint of this invention provides the powder coating material for electrostatic coating of a base material, and a powder is obtained by the above methods.
Still further, a first aspect of the present invention provides a pharmaceutical tablet comprising a tablet core and a powder coating material as defined above.
Furthermore, a first aspect of the present invention provides a method of coating a pharmaceutical tablet core with powder, the method holding the tablet core in proximity to a source of powder coating material in an electric field, and at least the core. This portion is held at a potential different from the potential of the coating material, and a potential difference is applied to guide the powder from the powder source in the direction of the tablet core and the core surface, and the powder coating material is applied.
Since the coating of the tablet core induces the powder material towards the tablet core as a result of the application of an electric field and at least the potential difference between the tablet core portion and the powder material, the point of arrival of the powder material is at least initially the tablet. Limited to the surface of the wick. If it is arranged only on the exposed surface, it is in the vicinity of the powder material and where there is an appropriate potential difference with respect to the powder material.
A special advancement of the method is that it can be carried out in a continuous process.
It is advantageous to transfer the tablet core by transfer means through an area proximate to the source of powder coating material. By transferring the tablet core, it can be ensured that the tablet core is handled gently throughout the coating process and that even the fragile tablet core is not damaged.
This method can be used to coat tablet cores that are fragile and cannot withstand conventional tablet coating methods. Thus, the present invention has made it possible to produce tablets having a conventional shape and having a wide range of compositions. Also, unconventional shaped tablets, for example, tablets that are not conventional circular surfaces but rather have opposite planes can be produced by the method of the present invention. Such flat tablets are usually very fragile and could not be painted by conventional methods. Furthermore, plane tablets are often joined together to form twin tablets and groups of tablets, which could not be properly painted by conventional coating methods.
The tablet core is held from the top close to the powder coating material source and the powder moves from above the source to the lower surface of the substrate.
The tablet core produced by the coating method specified above is simply a partial coating, and this coating method includes the following further steps, which are applied in the vicinity of the powder coating material source in an electric field. Holding the tablet core, maintaining at least a portion of the tablet core at a potential different from the potential of the coating material, applying a potential difference to direct the powder from the powder source toward the tablet core, and uncovering the uncoated surface of the tablet core It is to be painted with powder coating material. In this way, it is possible to easily apply to the entire surface of the tablet core, and it is also possible to apply different parts of the tablet core with different coating materials. For example, different colors can be applied to each opposite side of the tablet.
Furthermore, the 1st viewpoint of this invention provides the pharmaceutical tablet which gave electrostatic coating by the method specified above.
In accordance with the first aspect of the present invention, powder coating materials and coating methods have been developed, especially for pharmaceutical tablet core coatings and to address the harsh conditions that can be imposed on the material from the application of the coating. Although materials and methods have been developed that are suitable for pharmaceutical tablet core coatings, we have further expanded our thinking to other uses where the materials and methods can be used effectively. For example, in the pharmaceutical industry, the materials and methods can be used to paint other pharmaceutical products that are not taken orally, for example, pessaries, boogies or suppositories, or other pharmaceutical substrates.
According to a second aspect of the present invention, there is provided a powder coating material for electrostatic powder coating of a pharmaceutical substrate, the material having one or more of the following properties.
a) suitable for human and / or animal consumption;
b) consisting of at least two foreign components, preferably the particles consist of composite particles,
c) A thin film coating is formed by melting at a temperature of 250 ° C. or less at atmospheric pressure.
d) at least 30% by weight of the particles have a particle size ranging from 5 μm to 20 μm,
e) It is sensitive to movement under the action of electrostatic force, and its sensitivity is measured by the test method specified here.
It is particularly preferred that the powder coating material is a physiologically acceptable material and preferably a pharmaceutically acceptable material. The material can have other properties as described above in the description of the pharmaceutical tablet core coating material.
The present invention also provides a method for producing a powder coating material comprising at least two extraneous components for electrostatic coating of a substrate, the method comprising the step of simultaneously treating the at least two extraneous components. It is a waste.
Furthermore, the second aspect of the present invention provides a method of electrostatically coating a pharmaceutical substrate with the powder coating material specified above.
Here, when there is a description relating to a number% of particles having a specific size, such as a number% of particles, it is preferable that the particles have the same volume% of the particles of the size. Furthermore, when there is a description about the volume% particles, it is preferred that the particles have the same weight% particles.
By way of example, a method for coating a pharmaceutical tablet core and several powder coating materials suitable for coating a pharmaceutical tablet core will be described with reference to the accompanying drawings.
In the drawings, FIG. 1 schematically shows a side view of an apparatus for coating a tablet core, and FIG. 2 schematically shows a cross section of a drum of the apparatus of FIG.
The apparatus schematically illustrated in FIG. 1 is an apparatus for coating both sides of a pharmaceutical tablet core. The apparatus includes an inclined chute for supplying a tablet core that is connected to the first rotating drum 12. The drum 12 is made of steel and has a circular depression 14 (FIG. 2) on its outer surface. As will be described later, the tablet core is held in each recess by suction.
The drum 12 can rotate in the direction of the arrow. Near the circumference of the drum 12 and downstream of the tablet supply chute 10, there is a preparation position A containing an electrostatic spray gun 16, which covers the exposed surface of the tablet core with charged droplets emitted from the gun 16. To do. Downstream of the preparation position is the coating position B including the vibrating powder dish 18, which holds and fluidizes the core coating powder and recirculates in the coating area D. Downstream of the painting position is a melting position C including the heater 20. After passing through the melting position C, the coating core passes through a cooling position (not shown) where cooling air is induced on or around the tablet to cool the molten coating.
The second drum 12 ′ is close to the first drum 12, and the drum tightening portion is downstream of the melting position C. The second drum 12 'rotates opposite the first drum 12 as indicated by an arrow. The second drum 12 'is equipped with a preparation position A' including a gun 16 ', a coating position B' including a powder pan 18 ', a melting position C' including a heater 20 ', and a cooling position (not shown).
The tablet core collecting chute 22 is inclined downwardly away from the second drum 12 'downstream of the melting position C', and the coated tablet core is taken out and connected to the next processing and packaging process.
The first drum 12 will be described in detail with reference to FIG. The drum includes a rotatable skin 24 with a recess 14 on the outer surface of the skin. In FIG. 2, only five representative depressions are shown. In practice, a large number of depressions are evenly positioned in the circumferential row around the outer plate 24, and there are a number of circumferential rows across the width of the drum, where there is one continuous outside It can be seen that a plate or several outer plates fixed side by side are formed. The shape and dimensions of the indentations 14 on the drum are guaranteed such that when the tablet core is on the drum, one half of the core core and half the side wall depth are exposed. In the case of a round tablet core, a recess diameter close to the tablet core diameter is preferred. In some applications, the depth of the depression is exposed to the coating material particles so that it is at least 50% of the thickness of the core, exposing the first surface of the core, and then exposing the other surface. To completely cover the core.
Each indentation 14 on the drum is provided with an extraction arm 26 that is electrically isolated from the other indentations and extends radially inward, but ends in front of the center of the drum. The extraction arm 26 is attached to the inner surface of the outer plate 24 and rotates together with the outer plate 24. Each associated extraction arm 26 and depression 14 together form a moving electrode and charge the core in the depression. Each recess 14 has a core holding means that opposes an external force such as gravity, for example, a passage 28 passing through a wall connected to the suction connection pipe 30, and the suction connection pipe 30 does not rotate with the outer plate, Around a part of the periphery of the drum, it extends inward from immediately upstream of the lead supply chute close to the tightening portion between the first drum 12 and the second drum 12 ′.
The grounded fixed arched first electrode 32 is placed inside the drum at an angular position corresponding to the preparation position A. The fixed arched second electrode 34 having a potential difference with respect to the ground is placed inside the drum at an angular position corresponding to the painting position B. The arch outer surface of the fixed station is at the same radial distance from the center of the drum and becomes the free end of the extraction arm 26 of the moving electrode. As the outer plate 24 rotates, the moving electrode sequentially contacts the first and second fixed electrodes. The drum 12 is held by being connected to the same potential difference with respect to the ground as in the case of coating powder, preferably the ground potential, preferably the powder dish 18.
The second drum 12 ′ is configured in the same manner as the first drum, and includes a rotating outer plate having a recess, an extraction arm, first and second fixed electrodes, and a suction connection tube. The selection of the angular positions of the first and second fixed electrodes corresponds to the second preparation position A ′ and the second painting position B ′, and the suction connection pipe is tightened between the two drums close to the core collecting chute 22. It extends from just upstream of the department.
In use, the lead is continuously supplied to the lead supply chute 10. The lead descends the lead supply chute 10 and enters the recess 14 in the rotating outer plate 24 of the first drum 12. In this angular position, the recess is located on the suction connection tube 30, so that the core is held in the recess by suction by the passage 28 in the skin. The outer plate 24 continues to rotate and carries the core to the preparation position A, at which point the extraction arm 26 attached to the recess 14 contacts the first fixed electrode 32 and grounds the moving electrode, thus The core is held in the recess. As the grounded tablet core passes through the electrostatic spray gun 16, a capture-enhancing liquid such as a charged droplet of polyethylene glycol is sprayed onto its exposed surface.
The outer plate 24 continues to rotate, and when the tablet approaches the coating position B, the moving electrode 26 is removed from contact with the first fixed electrode 32 and brought into contact with the second fixed electrode 34. The exposed core surface treated with polyethylene glycol has a potential difference with respect to the ground, and the coating powder material is guided from the powder dish 18 to the core surface by electrostatic force. The potential generated by holding the drum surface and the powder at the same potential difference with respect to ground and the core at a different potential difference with respect to the ground causes the powder to be attracted to the core, but the drum surface is substantially free of powder. The state is guaranteed.
The outer plate 24 continues to rotate, removes the moving electrode 26 from contact with the second fixed electrode 34, carries the core to the melting position C, where the heater 20 melts the powder on the coating surface of the core, and forms a thin film. To form.
As the outer plate 24 continues to rotate, if the core leaves the melting position C and passes through the cooling position (not shown), the recess for carrying the core is no longer positioned on the suction connection pipe 30. The wick falls from the first drum 12 into a recess in the outer surface on the second drum 12 ', with its unpainted surface facing outward on the drum 12'. The depression is connected to the suction connecting pipe 30 of the second drum. As the lead moves between the second preparation position A ', the coating position B', the melting position C 'and the cooling position, the coating of the lead is completed. The coating powder material at the second painting position may be the same as or different from the coating powder material at the first painting position. In this way, tablets with differently painted surfaces can be produced. As the coated tablet approaches the collection chute, the dent carrying the wick disengages from the suction connection tube, the coated tablet falls into the chute and is further processed and packaged.
The drum itself is preferably at least 60 mm in diameter and not less than the minimum tablet diameter in width and rotates at least 1/2 rpm. The suction pressure of the suction connecting pipe is of a size effective for holding the tablet against gravity, and is preferably 0.2 to 0.6 bar under atmospheric pressure.
In the electrostatic spray guns 16 and 16 ′ at the preparation positions A and A ′, a semiconductive non-evaporable fluid, such as polyethylene glycol or an aqueous solution thereof, has an inner diameter of 0.05 to 2 mm at a speed of 0.1 to 1 ml / min. Supplied to steel capillaries. As each core on the drum passes through the gun, the capillary is connected to a current limited high voltage with a potential difference to ground (up to 50 kV at 30-100 μA), and from the capillary to the core on the drum, A spray of charged droplets is emitted. Since the core on the drum is grounded at the ready position, charged droplets are induced by the electric field between the capillary and the core, reach the exposed surface of the core and are captured there. The core is held at the preparation position with a potential difference with respect to ground, but only if the core has a potential difference with respect to the capillary. In this case, the fixed arched electrode 32 has a potential difference with respect to the ground. As each core leaves the preparation position, the supply of droplets from each capillary is controlled by turning off the voltage and grounding the capillary through a resistor (1-10 MΩ). This method sharpens the blockage of the droplets between the tablet cores.
At the coating positions B and B ', the powder coating material is supplied to the vibration dishes 18 and 18' by the vibration feeder. On each dish, a leveling plate is used to keep the powder height constant in the dish. The powder is vibrated and continuously recirculated. Said dish may be made of plastic material with metal pieces grounded under an arc swept by a tablet core on each drum, or may be made of metal. A new method of particle charging is triboelectric charging. The dish is preferably 50 to 150 mm long and 3 to 40 mm wide. If more than one dish is used to provide a two-color or multicolored surface or a surface having one or more polymer compositions, the dimensions of the dish can be changed accordingly. The tablet core is charged with a voltage of 3-15 kV with a limiting current up to 5 μA.
In melting or drying positions C and C ', energy is applied to the core surface to melt the powder and provide a uniform coating on the exposed surface of the core. Preferably, the energy is provided by focused irradiation in the infrared region. Energy performance requirements are largely determined by the coating material. After melting or drying, the coating is fixed in a cooling process using a blower.
A preferred coating device according to the present invention is capable of painting up to 300,000 tablet cores per hour.
Examples of powder coating materials suitable for use in the tablet core coating method described above with reference to FIGS. 1 and 2 are described below.
Example 1
The dry powder coating material was prepared by the following method.
(A) Samples containing the following compounds (wt%) were pre-mixed using a high shear mixer.
55.5% Udolite RS ™ (ammonio-methacrylate copolymer fine powder)
18.5% polyethylene glycol (high molecular weight: about 20000)
15.0% titanium dioxide
5.0% aluminum rake
5.0% sodium lauryl sulfate
0.5% Exprotab ™ (starch glycolate sodium salt)
0.5% Aerosil 200 ™ (colloidal silicon dioxide)
Prior to mixing, the particle size of each component of the sample was as follows.
Titanium dioxide 50% by volume is 5μm or less
Aluminum lake 50% by volume is less than 1μm
Sodium lauryl sulfate 50% by volume is 100μm or less
Eudolite 50% by volume is 40μm or less
Polyethylene glycol 50% by volume is 60 to 70 μm
(B) The previous mixture was wet granulated by the following method. Water was gradually added to the mixture obtained in (a) above and mixed for several minutes in a high shear mixer to obtain a granular mixture. The weight of the added water was about 10-15% of the premix weight.
(C) The granular mixture obtained in step (b) above is dried in a fluid bed dryer at a temperature of about 45 ° C. for about 20-30 minutes to a moisture content of 3% by weight or less (as drying loss) A material having (measurement) was obtained.
(D) The small particles obtained in step (c) were impact pulverized and then finely pulverized using a fluid energy pulverizer to obtain a powder. The powder had a size of 50% by volume of particles of 20 μm or less and almost 100% by volume of 60 μm or less. The peak of the particle size distribution was observed at about 10 μm.
The powder was sensitive to movement under the action of the electrostatic force specified above.
(E) A tablet core was coated with the powder using the method and apparatus described previously. No pretreatment with the trapping power enhancing liquid was performed. The coating powder on the tablet core was heated to a temperature of about 130 ° C. for about 5 seconds using an infrared source to melt the powder coating on the tablet core surface. The resulting coating had good opacity, was smooth, glossy and brightly colored. The coating thickness was 100 μm or less.
The particle size distribution of the powder particles prepared in the step (d) was measured.
100% 57.25 μm or less
70.29% 22.04 μm or less
5.58% 1.52 μm or less
About 50% of the particles were 15.05 μm to 32.29 μm in size.
About 35% of the particles were 18.21 μm to 32.29 μm size.
The average particle size was 19.17 μm (calculated in one way).
Example 2
Using a sample containing the following compound (% by weight)
59.6% Eudolite RS (ammonio-methacrylate copolymer)
19.9% Crucell ™ (hydroxypropyl cell sauce)
15.0% titanium dioxide
5.0% aluminum rake
0.5% croscarmellose sodium (cross-linked sodium carboxymethyl cellulose)
A powder coating material was prepared by the method described in steps (a) to (d) of Example 1. As described in step (e) of Example 1, the powder material was applied to the tablet core surface and melted. The resulting coating was smooth, highly glossy, had a strong color and good opacity. This coating was judged to have a higher gloss than that expected for a conventional thin film-coated tablet core.
Example 3
Using a sample containing the following compound (% by weight)
39.75% Eudolite RS (ammonio methacrylate copolymer)
39.75% Crucell (hydroxypropyl cell sauce)
15.0% titanium dioxide
5.0% aluminum rake
0.5% Aerosil 200 (colloidal silicon dioxide)
A powder coating material was prepared by the method described in steps (a) to (d) of Example 1. As described in step (e) of Example 1, the powder material was applied to the tablet core surface and melted. The resulting coating was smooth, glossy, had a strong color and good opacity.
Example 4
Using a sample containing the following compound (% by weight)
60.0% Eudolite RS (ammonio methacrylate copolymer)
20.0% Glycerol monostearate
15.0% titanium dioxide
5.0% aluminum rake
A powder coating material was prepared by the method described in steps (a) to (d) of Example 1. As described in step (e) of Example 1, the powder material was applied to the tablet core surface and melted. The resulting coating was smooth, matte, had a strong color and good opacity.
Example 5
Using a sample containing the following compound (% by weight)
60.0% Eudolite RS (ammonio methacrylate copolymer)
20.0% Xylitol
15.0% titanium dioxide
5.0% aluminum rake
A powder coating material was prepared by the method described in steps (a) to (d) of Example 1. As described in step (e) of Example 1, the powder material was applied to the tablet core surface and melted. The resulting coating was semi-gloss, had a strong color and good opacity.
Example 6
Using a sample containing the following compound (% by weight)
46.5% Eudolite RS (ammonio methacrylate copolymer)
28.0% Crucell (hydroxypropyl cell sauce)
15.0% titanium dioxide
5.0% aluminum rake
5.0% polyethylene glycol 6000
0.5% Aerosil 200 (colloidal silicon dioxide)
A powder coating material was prepared by the method described in steps (a) to (d) of Example 1. As described in step (e) of Example 1, the powder material was applied to the tablet core surface and melted. The resulting coating was smooth, had a strong color and good opacity.
Example 7
A sample containing the following compound (% by weight)
56.25% polyethylene glycol
20.0% Titanium dioxide
18.75% Eudolite RS (ammonio methacrylate copolymer)
5.0% aluminum rake
Formulated using a high shear mixer. In the pre-formulation state, polyethylene glycol and eudolite are at least 50% by volume of particles having a size of 100-200 μm and similar particle sizes, and at least 50% by volume of titanium dioxide and aluminum lake are less than 1 μm. Had a size.
(B) The dried blended mixture was pulverized to obtain a powder material having a particle size of 300 μm or less in which at least 50% by volume of the particles had a size of 100 to 200 μm.
(C) The material was applied to the tablet core using the method and apparatus described above, including a pretreatment spray of polyethylene glycol. The coating powder on the tablet core was heated to a temperature of about 130 ° C. for about 5 seconds using an infrared source to melt the powder coating on the tablet core surface. The resulting coating was smooth, high gloss, strong color and good opacity. This coating was judged to have a higher gloss than that expected for a conventional thin film-coated tablet core.
Example 8
A sample containing the following compound (% by weight)
56.25% polyethylene glycol
20.0% Titanium dioxide
18.75% Eudolite RS (ammonio methacrylate copolymer)
5.0% aluminum rake
Dry blended using a high shear mixer and the blended mixture was milled as described in Example 7, step (b). In addition, the said component had the particle size similar to the particle size as described in Example 7 before the preparation (polyethylene glycol has the same particle size as that of Udrite). The resulting material was applied to the tablet core as described in step (c) of Example 7. The resulting coating was smooth, high gloss, strong color and good opacity. This coating was judged to have a higher gloss than that expected for a conventional thin film-coated tablet core.
In the above embodiment, all the components are in the form of a particulate solid material, but the powder coating material may contain a liquid-shaped component.

Claims (39)

A method of electrostatically coating a pharmaceutical substrate with a powder material, wherein the powder material is pharmaceutically acceptable and contains composite particles, each composite particle having a first component having different physical and / or chemical properties And at least a second component,
The first component is melted at a temperature of 250 ° C. or lower to form a continuous thin film on the surface of the substrate, and polyoxyethylene, sugar alcohol, unsaturated or saturated fatty acid or ester thereof, cellulose derivative, polyethylene glycol, wax or oil. One or more compounds selected from the group consisting of alcohols of waxes or oils, poloxamers, alkyl phthalates, citric acid or esters thereof,
The second component imparts electrostatic properties to the powder material, and includes acrylic acid, polymers and copolymers of acrylic acid and derivatives thereof, polyalkene and derivatives thereof, polyvinyl alcohol and esters, cellulose and derivatives thereof, polylactide, polyglycolide, polyhydroxy Including one or more compounds selected from the group consisting of butyrate, polyhydroxyvalerate, ethylene vinyl acetate copolymer, polyanhydride, polyethylene oxide,
The method, wherein after coating a base material with the powder material, the powder material is melted to form a continuous thin film fixed to the base material. The method of claim 1, wherein at least 50% by weight of the material particles are composite particles. The method of claim 2, wherein all particles are composite particles. 4. A method according to any one of claims 1 to 3, wherein at least 30% by volume of the particles of the powder have a particle size in the range of 5 [mu] m to 25 [mu] m. 5. A method according to any one of the preceding claims, wherein the particles of at least 90% by volume of material have a particle size of 50 [mu] m or less. 6. A method according to any one of the preceding claims, wherein the particles of at least 50% by volume of material have a particle size of at least 5 [mu] m. The method according to any one of claims 1 to 6, wherein the first component comprises a cellulose derivative, polyoxyethylene, polyethylene glycol, a fatty acid or an ester thereof, or two or more of these compounds. 8. A method according to any one of the preceding claims, wherein the material contains at least 10% by weight of the first component, based on its weight. 9. A method according to any one of claims 1 to 8, wherein the second component comprises a polymer or copolymer of a derivative of acrylic acid, a polyvinyl ester or polyethylene oxide or two or more of these compounds. 10. A method according to any one of the preceding claims, wherein the material contains at least 10% by weight of the second component, based on its weight. 11. A method according to any one of the preceding claims, wherein the material comprises a dispersant component for improving the dispersion of the first component and the second component. 12. A method according to any one of the preceding claims, wherein the material comprises at least one component selected from a lubricant, disintegrant, opacifier, colorant, flavor. Material has a resistivity in the range of 10 ⁸ ~10 ¹⁶ Ωm, a method of any one of claims 1 to 12. 14. A method according to any one of the preceding claims, wherein the material can be charged triboelectrically and / or by corona charging. The method according to any one of claims 1 to 14, wherein the material is an electret, a magnet or a paramagnetic material. 16. A method according to any one of claims 1 to 15, wherein the composite particles have the form of individually separated particles. 16. A method according to any one of the preceding claims, wherein the composite particles have the form of agglomerates or agglomerates of individually separated particles of different components. 18. A method according to any one of claims 1 to 17, wherein the powder coating material comprises an active material. Active materials in powder coating materials include acid digestion / exercise inducers, laxatives, antidiarrheals, colon and rectal drugs, pancreatic enzymes and bile acids, antiarrhythmic drugs, antianginal drugs, diuretics, antihypertensive drugs , Anticoagulant, antithrombotic, fibrinolytic, hemostatic, fat deficiency, anti-anemic / neutropenia, hypnotic, anxiolytic, antipsychotic, antidepressant, antiemetic, antispasmodic , CNS stimulant, analgesic, antipyretic, anti-migraine, nonsteroidal anti-inflammatory, anti-ventilant, muscle relaxant, neuromuscular, steroid, hypoglycemic, hyperglycemic, diagnostic, Antibiotics, antifungal drugs, antimalarial drugs, antiviral drugs, immunosuppressive drugs, nutritional drugs, vitamins, electrolytes, appetite suppressants, desire suppressants, bronchodilators, expectorants, antitussives, mucolytic drugs, depression One or more selected from blood removal agents, antiglaucoma agents, oral contraceptives, and / or antitumor agents The method of claim 18 comprising the compound. 20. A method according to claim 18 or claim 19, wherein the powder coating material comprises at least 0.5% by weight of active material, based on its weight. 21. A method according to any one of claims 18 to 20, wherein the coated substrate constitutes an orally ingested pharmaceutical product. 21. A method according to any one of claims 18 to 20, wherein the coated substrate constitutes a medicinal product that is not taken orally. 23. A method according to claim 21 or 22, wherein the pharmaceutical product forms a dosage unit selected from the group consisting of tablets, pellets, capsules, globules, pessaries, bougies and suppositories. The method according to claim 21, wherein the substrate is a tablet core. 25. A method according to any one of claims 18 to 24, wherein the pharmaceutical substrate comprises an active material that is different from the powder material. 25. A method according to any one of claims 18 to 24, wherein the pharmaceutical substrate does not comprise an active material. 25. A method according to any one of claims 18 to 24, wherein the pharmaceutical substrate comprises the same active material as the powder coating material. 18. A method according to any one of claims 1 to 17, wherein the substrate is a pharmaceutical product that is taken orally. Holding the substrate in close proximity to the powder coating material source, maintaining the substrate surface at a potential different from that of the coating material, applying the potential to move the powder from the powder source toward the substrate; and The method according to any one of claims 1 to 28, wherein the substrate surface is coated with a powder coating material. 30. The method of claim 29, wherein the substrate is charged when the substrate is proximate to the powder coating material source. 32. The method of claim 30, wherein the powder coating material source is grounded. 32. A method according to any one of claims 29 to 31 wherein the substrate is held upward and the powder moves upward from the source towards the substrate lower surface. 33. A method according to any one of claims 29 to 32, wherein the pretreatment composition is applied to the substrate surface prior to holding the substrate in proximity to the powder coating material source. Hold the painted substrate close to the powder coating material supply source, expose the unpainted surface of the substrate and maintain the substrate surface at a potential different from the potential of the coating material, and apply the potential to powder the powder 34. A method according to any one of claims 29 to 33, further comprising moving from a source toward the substrate and painting the exposed surface of the substrate with a powder coating material. Medical drug to unacceptable treatment by can form a thin film coating and includes composite particles, each composite particle comprises at least a first component and a second component having different physical and / or chemical properties,
The first component is melted at a temperature of 250 ° C. or lower to form a continuous thin film on the surface of the substrate, and polyoxyethylene, sugar alcohol, unsaturated or saturated fatty acid or ester thereof, cellulose derivative, polyethylene glycol, wax or oil. One or more compounds selected from the group consisting of alcohols of waxes or oils, poloxamers, alkyl phthalates, citric acid or esters thereof,
The second component imparts electrostatic properties to the powder material, and includes acrylic acid, polymers and copolymers of acrylic acid and derivatives thereof, polyalkene and derivatives thereof, polyvinyl alcohol and esters, cellulose and derivatives thereof, polylactide, polyglycolide, polyhydroxy Including one or more compounds selected from the group consisting of butyrate, polyhydroxyvalerate, ethylene vinyl acetate copolymer, polyanhydride, polyethylene oxide,
Use of a powder coating material in a pharmaceutical substrate electrostatic coating, wherein at least 30% by volume of the particles of the powder have a particle size in the range of 5 to 25 μm. 36. Use according to claim 35, wherein the coating material is as specified in any of claims 2 to 22. Medical drug to unacceptable treatment by can form a thin film coating and includes composite particles, each composite particle comprises at least a first component and a second component having different physical and / or chemical properties,
The first component is melted at a temperature of 250 ° C. or lower to form a continuous thin film on the surface of the substrate, and polyoxyethylene, sugar alcohol, unsaturated or saturated fatty acid or ester thereof, cellulose derivative, polyethylene glycol, wax or oil. One or more compounds selected from the group consisting of alcohols of waxes or oils, poloxamers, alkyl phthalates, citric acid or esters thereof,
The second component imparts electrostatic properties to the powder material, and includes acrylic acid, polymers and copolymers of acrylic acid and derivatives thereof, polyalkene and derivatives thereof, polyvinyl alcohol and esters, cellulose and derivatives thereof, polylactide, polyglycolide, polyhydroxy Including one or more compounds selected from the group consisting of butyrate, polyhydroxyvalerate, ethylene vinyl acetate copolymer, polyanhydride, polyethylene oxide,
Use of a powder coating material in which the material also comprises an active material in electrostatic coating of a pharmaceutical substrate . Coating material is based on claims 19-22, use as claimed in claim 37. 39. Use according to any one of claims 35 to 38 , wherein the substrate is a pharmaceutical product that is taken orally.

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